Impact of Deep Neuromuscular Blockade During Total Hip Replacement Surgery on Postoperative Recovery and Immune Function

Phase 4

Recruiting

• Conditions: Quality of Life; Postoperative Complications; Neuromuscular Blockade; Innate Inflammatory Response
• Interventions: Drug: Rocuronium Bromide

• Registration Number: NCT05562999
• Lead Sponsor: Radboud University Medical Center

Brief Summary

Monocenter randomized controlled trial to compare the effect of deep neuromuscular blockade (NMB) versus moderate NMB during total hip replacement surgery on postoperative quality of recovery and innate immune function.

Detailed Description

Rationale: Neuromuscular blockade agents (NMB) may enable surgeons to optimize exposure during hip surgery. With an increasing depth of NMB, manipulation of muscles and adjunctive tissues may be easier, therefore reducing damage to muscles and adjunct tissues. Accumulating evidence exists that the use of deep NMB in laparoscopic surgery is associated with a better quality of recovery and lower pain scores. However, whether this accounts for open surgery is still unknown.

In addition, surgery is associated with postoperative immune suppression. Surgical stress and damage cause the release of Danger Associated Molecular Patterns (DAMPs). After trauma and sepsis, the release of DAMPs is associated with immune paralysis and a higher susceptibility to infectious complications. Previous research indicates that DAMPS are the origin of postoperative immune suppression. The use of deep NMB in hip surgery may reduce surgical damage and thereby lead to a better quality of recovery and secondarily a better preservation of immune cell function.

Primary objective: To establish the relationship between the use of deep neuromuscular blockade (NMB) versus moderate NMB and the quality of recovery after total hip replacement surgery (THR) Secondary objective: To establish the relationship between the use of deep NMB versus moderate NMB and innate immune function after THR surgery

Study design: A monocenter, blinded, randomized controlled clinical trial

Study population: adults who are scheduled for primary or secondary hip replacement surgery under general anaesthesia.

Intervention: Patients will be randomized between a deep NMB (post tetanic count (PTC) 1-2) and moderate NMB (Train-of-four (TOF) 1-2)

Primary endpoint: Quality of Recovery score (QoR-40) at postoperative day 1.

Secondary endpoints: postoperative innate immune function, QoR-40 at postoperative day 30, 30-day postoperative (infectious) complications, postoperative pain scores and opioid consumption

Study Timeline

• Study First Submitted: 2022-09-28
• Study First Submitted QC: 2022-09-28
• Study First Posted: 2022-10-03
• Study Start: 2022-11-18
• Status Verified: 2023-10
• Last Update Submitted: 2024-06-24
• Last Update Posted: 2024-06-25
• Primary Completion: 2024-08
• Study Completion: 2024-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Age of 18 years or older
• Scheduled for total hip replacement surgery under general anaesthesia
• Informed consent obtained

Exclusion Criteria

• Insufficient control of the Dutch language to read the patient information and to fill out de questionnaires
• Known or suspected hypersensitivity to rocuronium or sugammadex
• Deficiency of vitamin K dependent clotting factors or coagulopathy
• Severe renal disease (creatinine clearance <30 ml/min), including patients on dialysis
• Severe liver disease (Child-Pugh Classification C)
• Known or suspected neuromuscular disorders impairing neuromuscular function
• Women who are or may be pregnant or currently breastfeeding
• Chronic use of psychotropic drugs
• Use of immunomodulatory medication

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Deep neuromuscular blockade	Rocuronium Bromide	Participant will receive deep neuromuscular blockade (PTC 1-2)
Moderate neuromuscular blockade	Rocuronium Bromide	Participant will receive moderate neuromuscular blockade (TOF 1-2)

Primary Outcome Measures

Name	Time	Method
Quality of Recovery 40 (QoR-40) questionnaire score	Postoperative day 1	40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery)

Secondary Outcome Measures

Name	Time	Method
Immune function represented by ex-vivo IL-10 production capacity	Postoperative day 1	Ex-vivo IL-10 production capacity upon whole blood LPS stimulation
Postoperative complications	30 postoperative days	postoperative complications scored by Clavien-Dindo classification; grade 0 (no deviation from ideal) grade 5 (death of patient)
Immune function represented by IL-10	Postoperative day 1	Serum cytokine IL-10 level
Immune function represented by TNF-a	Postoperative day 1	Serum cytokine TNF-a level
Immune function represented by ex-vivo IL-6 production capacity	Postoperative day 1	Ex-vivo IL-6 production capacity upon whole blood Lipopolysaccharide(LPS) stimulation
Quality of Recovery 40 (QoR-40) questionnaire score	Postoperative day 30	40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery)
Infectious postoperative complications	30 postoperative days	Postoperative infectious complications scored the definitions of the StEP-COMPAC group initiative
Immune function represented by serum cytokine	Postoperative day 1	Serum cytokine IL-6 level
Pain score by numeric pain rating (NRS) scale	During hospital admission up to 3 days postoperative	pain scores with NRS 0 (no pain) to 10 (severe pain)
Analgesia consumption	During hospital admission up to 3 days postoperative	non-cumulative and cumulative opioid use per day in morphine equivalent

Trial Locations

Locations (1)

Radboudumc; 🇳🇱 Nijmegen, Netherlands